Sustained Versus Minimal GLP ‐1 Receptor Agonist Exposure and Metabolic Outcomes in Older Adults Without Diabetes

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Abstract
Aims: To compare changes in body mass index (BMI) categories after sustained versus minimal glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) exposure in older adults with obesity and without diabetes. A secondary aim was to compare changes in glycated haemoglobin (HbA1c) categories among those with paired HbA1c measurements. Materials and Methods: Retrospective cohort study within Clalit Health Services, Israel. Adults aged ≥ 65 years without diabetes, with baseline BMI ≥ 30 kg/m 2 and paired BMI measurements, were classified as minimal (1–2 dispensations) or sustained (≥ 3) exposure. The primary outcome was BMI category improvement. Secondary outcomes were relative BMI change, HbA1c category change in the paired‐HbA1c subset, and incident diagnosed diabetes. BMI improvement was modelled by logistic regression adjusted for age, sex, socioeconomic status and comorbidity. Results: Of 13 387 patients (69% female), 11 121 (83%) had sustained and 2266 (17%) minimal exposure. BMI category improved in 55% of the sustained versus 30% of the minimal group ( p < 0.001; median change −8% vs. −2%). Among 7392 with paired HbA1c, HbA1c improved in 34% versus 20% (sustained vs. minimal; p < 0.001), and 65% versus 37% of those with prediabetes became normoglycaemic. Diabetes diagnosis was less frequent with sustained exposure (2.5% vs. 5.3%; p < 0.001). Adjusted for measured confounders, sustained exposure was associated with BMI improvement (OR: 2.77, 95% CI: 2.51–3.06). Conclusions: Among older adults with obesity and without diabetes, sustained versus minimal GLP‐1 RA exposure was associated with greater improvement in BMI and HbA1c categories and a lower incidence of diabetes. These findings describe observed changes after treatment initiation, not a proven causal treatment effect.

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